The use of implant devices is becoming important with regard to the administration of drugs or pharmaceuticals particularly to animals raised for the human food supply. In general, these devices containing the pharmaceutical or drugs to be administered are subcutaneously implanted in the animal and the pharmaceuticals or drugs are administered to the animal over a prolonged period of time in a predetermined and controlled quantity. By use of implant devices, it is not necessary to repeatedly administer the pharmaceutical material daily to the animal in question. In this way whole herds of cattle or other animals raised for human food purposes can be simultaneously implanted with a device containing a pharmaceutical so that device releases the pharmaceutical to the animal over a prolonged period of time.
It has been difficult to construct implants with a zero order timed dependence rate of release. A zero order timed dependence rate of release occurs when a constant controlled amount of the pharmaceutical is released daily to the animal. In most cases, implants provide an initial burst of drug release which slowly tapers off with time. Such variable rates of release are extremely disadvantageous, since they do not provide the proper controlled dosing to be administered to the animal. Therefore, it has been long desired to provide a drug delivery device for subcutaneous implantation, which can release the drug with minimum initial burst and at a controlled rate which does not substantially vary with time.
Various devices have been proposed for solving this problem. However, none have been entirely satisfactory. As set forth in U.S. Pat. No. 3,710,795, Higuchi et al., Jan. 16, 1973, these devices generally constitute an inner matrix carrying the pharmaceutical material or drug to be administered, and a polymeric membrane permeable to the passage of this therapeutic material or drug by diffusion. In the device of Higuchi, et al., the matrix is sealed within a heat shrinkable stretched polymeric membrane formed about the matrix. As this matrix contracts, some of the drug is removed therefrom, forming gas pockets or voids which can slow-up the release of the drug through the membrane and introduce an uncontrollable factor into the drug release mechanism.
In order to solve this problem, Chien, et al. in U.S. Pat. Nos. 3,946,106, Mar. 23, 1976; 3,992,518, Nov. 6, 1976; and 4,053,580, Oct. 11, 1977 disclose utilizing a pharmaceutical delivery device with a heat shrinkable membrane where the matrix contains microsealed compartments containing the pharmaceutical in a hydrophilic solvent system. This system, as disclosed in U.S. Pat. No. 4,472,394, Sep. 18, 1984--Peterson, is used for administering steriods, in particular 17-acetoxy-11.beta.-methyl-norpregn-4-ene-20-dione (norgestomet) for controlling estrus in female cattle. It has been found that while the matrix of this delivery system does not shrink in volume due to the presence of microsealed compartments, the diffusion rate of the pharmaceutical from these compartments is insufficient to allow a controlled rate of release of the drug or pharmaceutical for an extended period of time.